Author:
Aziz Nobia,Ullah Mukhtar,Rashid Abdur,Hussain Zubair,Shah Khadim,Awan Azeem,Khan Muhammad,Ullah Inam,Rehman Atta Ur
Abstract
Abstract
Background
Retinitis pigmentosa (RP) is one of the most frequent hereditary retinal diseases that often starts with night blindness and eventually leads to legal blindness. Our study aimed to identify the underlying genetic cause of autosomal recessive retinitis pigmentosa (arRP) in a consanguineous Pakistani family.
Methods
Following a detailed ophthalmological examination of the patients by an ophthalmologist, whole-exome sequencing was performed on the proband’s DNA to delineate the genetic cause of RP in the family. In-depth computational methods, in-silico analysis, and familial co-segregation study were performed for variant detection and validation.
Results
We studied an inbred Pakistani family with two siblings affected by retinitis pigmentosa. The proband, a 32 years old female, was clinically diagnosed with RP at the age of 6 years. A classical night blindness symptom was reported in the proband since her early childhood. OCT report showed a major reduction in the outer nuclear layer and the ellipsoid zone width, leading to the progression of the disease. Exome sequencing revealed a novel homozygous missense mutation (c.938C > T;p.Thr313Ile) in exon 12 of the PDE6B gene. The mutation p.Thr313Ile co-segregated with RP phenotype in the family. The altered residue (p.Thr313) was super conserved evolutionarily across different vertebrate species, and all available in silico tools classified the mutation as highly pathogenic.
Conclusion
We present a novel homozygous pathogenic mutation in the PDE6B gene as the underlying cause of arRP in a consanguineous Pakistani family. Our findings highlight the importance of missense mutations in the PDE6B gene and expand the known mutational repertoire of PDE6B-related RP.
Publisher
Springer Science and Business Media LLC
Subject
Ophthalmology,General Medicine
Reference44 articles.
1. Verbakel SK, van Huet RAC, Boon CJF, den Hollander AI, Collin RWJ, Klaver CCW, et al. Non-syndromic retinitis pigmentosa. Prog Retin Eye Res. 2018;66:157–86.
2. Sen P, Bhargava A, George R, Ramesh SV, Hemamalini A, Prema R, Kumaramanickavel G, Vijaya L. Prevalence of retinitis pigmentosa in South Indian population aged above 40 years. Ophthalmic Epidemiol. 2008;15(4):279–81.
3. Xu L, Hu L, Ma K, Li J, Jonas JB. Prevalence of retinitis pigmentosa in urban and rural adult Chinese: the Beijing Eye Study. 2006. p. 865–6.
4. Campochiaro PA, Mir TA. The mechanism of cone cell death in Retinitis Pigmentosa. Prog Retin Eye Res. 2018;62:24–37.
5. Zhang L, Li Y, Qin L, Wu Y, Lei B. Autosomal Recessive Retinitis Pigmentosa associated with three novel REEP6 variants in Chinese population. Genes (Basel). 2021;12(4):537.
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